West Nile virus an arthropod-borne flavivirus, has emerged in recent years as a deadly health threat to not only humans, but also to other animal species such as horses and birds. New York was the first area in North American to report cases of West Nile virus infections.
West Nile virus infection in humans has been found previously only in Africa, the Middle East and Eastern Europe. The virus is transmitted to humans and several animal species by mosquitoes which acquire the virus by feeding on infected birds. It is not known how West Nile virus was transmitted into the United States, however, scientists believe that it may have been transmitted through immigration or importation of an infected human, bird or mosquito from an endemic area.
Nevertheless, West Nile virus remains a continued threat to public health. Epidemiologic and virologic studies indicate that live virus persists in mosquito and bird populations. Mosquito control measures were implemented in New York, New Jersey and Connecticut, yet new cases of West Nile virus are being diagnosed. Certain populations are still being exposed to West Nile virus. For example, West Nile virus sero-prevalence studies in Queens, N.Y. indicate that 2.6% of the population, age 5 or older, had evidence of prior infection. Thus, a large portion of the population in Queens, and probably a larger portion in surrounding areas, remains susceptible to West Nile virus.
Among infected humans, approximately one in every 150 to 300 become ill with fever, myalgia and possible rash. Among those who are symptomatic, approximately 10-15% will have evidence of meningitis (headache, stiff neck) or encephalitis (change of mental status, peripheral neurologic abnormalities, muscle weakness). Though most humans with meningitis or encephalitis in New York were over age 50, older age was not associated with meningoencephalitis among 393 cases reported in the 1996 Romanian outbreak. However, almost all fatalities have occurred among humans over the age of 50. Underlying preexisting medical conditions were present in several fatal cases in New York, but were not risk factors for meningoencephalitis in Romania. The fatality rate among patients with central nervous system infection was 5% in Romania and 11% in New York. Fatalities have been due to prolonged central nervous system dysfunction requiring ventilatory support and leading to secondary complications. Prolonged neurologic symptoms have occurred in survivors of encephalitis.
Prior to the New York outbreak, fatal infection in birds (i.e. crows) was unusual. The New York strain of West Nile virus is most closely related to an isolated virus from a dead goose in Israel where increased pathogenicity of West Nile virus for birds was also noted.
The diagnosis of acute West Nile virus infection in humans is established by the presence of IgM antibody in serum or cerebrospinal fluid, a four-fold increase in antibody by ELISA or neutralization, or identification of West Nile virus RNA in brain tissue by polymerase chain reaction, or viral isolation. Occasionally, viremia (virus is in blood) occurs, but isolation of West Nile virus from blood has been uncommon.
To date, no effective prevention or treatment of West Nile virus infection exists. Until the present invention, prevention or treatment of West Nile virus infection was merely supportive (i.e. anti-pyretics are given to keep fever down, fluids, antibiotics for secondary bacterial infection, respiratory support as necessary, etc. One author in an abstract described activity of ribavirin against West Nile virus infection in mice. To date, ribavirin has not been used in the prevention or treatment of West Nile virus in humans.
Ribavirin and interferon alpha-2b are active against hepatitis C virus which is a member of the genus Flavivirus. West Nile virus is also a member of the genus Flavivirus. However, to date ribavirin in combination with interferon alpha-2b or interferon alpha-2b has not been used to prevent or treat West Nile virus infection in animals.
Based on the foregoing, there is a need for effective methods of preventing or treating deadly West Nile virus and other infections in humans and animals. Accordingly, there is also a need for effective combination therapy to prevent or treat West Nile virus.